scholarly journals Hyperammonemic Coma in an Adult due to Ornithine Transcarbamylase Deficiency

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Daniel L. Roberts ◽  
David A. Galbreath ◽  
Bhavesh M. Patel ◽  
Timothy J. Ingall ◽  
Amer Khatib ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Urea Cycle ◽  
Altered Mental Status ◽  
Ornithine Transcarbamylase ◽  
University Teaching ◽  
Ornithine Transcarbamylase Deficiency ◽  
Inborn Errors ◽  
Continuous Venovenous Hemodialysis ◽  
Biochemical Testing ◽  
Sodium Phenylacetate

Objective. To report an unusual cause of coma in an adult.Design. Case report.Setting. University teaching hospital.Patient. A previously healthy 53-year-old man initially presented with altered mental status and progressed to coma. He was found to be substantially hyperammonemic and did not improve with lactulose therapy and continuous venovenous hemodialysis.Results. Biochemical testing revealed previously undiagnosed ornithine transcarbamylase deficiency, and the patient responded to arginine, sodium phenylacetate, and sodium benzoate.Conclusion. Even in adult patients with no known history, inborn errors of metabolism must be considered in the differential diagnosis of unexplained coma. Defects of the urea cycle can present with an unprovoked hyperammonemic coma.

Characteristics of NO cycle coupling with urea cycle in non-hyperammonemic carriers of ornithine transcarbamylase deficiency

2013 ◽  
Vol 109 (3) ◽  
pp. 251-254 ◽  
Author(s):  
Hironori Nagasaka ◽  
Tohru Yorifuji ◽  
Hiroto Egawa ◽  
Ayano Inui ◽  
Tomoo Fujisawa ◽  
...  
Keyword(s):  
Urea Cycle ◽  
Ornithine Transcarbamylase ◽  
Ornithine Transcarbamylase Deficiency

scholarly journals Management of late onset urea cycle disorders—a remaining challenge for the intensivist?

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Redant ◽  
A. Empain ◽  
A. Mugisha ◽  
P. Kamgang ◽  
R. Attou ◽  
...  
Keyword(s):  
Cerebral Edema ◽  
Urea Cycle ◽  
Ornithine Transcarbamylase ◽  
Main Body ◽  
Urea Cycle Disorders ◽  
Ornithine Transcarbamylase Deficiency ◽  
Early Management ◽  
Metabolic Encephalopathy ◽  
Definitive Therapy ◽  
Cycle Disorders

Abstract Background Hyperammonemia caused by a disorder of the urea cycle is a rare cause of metabolic encephalopathy that may be underdiagnosed by the adult intensivists because of its rarity. Urea cycle disorders are autosomal recessive diseases except for ornithine transcarbamylase deficiency (OTCD) that is X-linked. Optimal treatment is crucial to improve prognosis. Main body We systematically reviewed cases reported in the literature on hyperammonemia in adulthood. We used the US National Library of Medicine Pubmed search engine since 2009. The two main causes are ornithine transcarbamylase deficiency followed by type II citrullinemia. Diagnosis by the intensivist remains very challenging therefore delaying treatment and putting patients at risk of fatal cerebral edema. Treatment consists in adapted nutrition, scavenging agents and dialysis. As adults are more susceptible to hyperammonemia, emergent hemodialysis is mandatory before referral to a reference center if ammonia levels are above 200 µmol/l as the risk of cerebral edema is then above 55%. Definitive therapy in urea cycle abnormalities is liver transplantation. Conclusion Awareness of urea cycle disorders in adults intensive care units can optimize early management and accordingly dramatically improve prognosis. By preventing hyperammonemia to induce brain edema and herniation leading to death.

Metabolic Disorders

2016 ◽  
Author(s):  
Lance Rodan
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Urea Cycle ◽  
Acid Oxidation ◽  
Catabolic Pathway ◽  
Peroxisomal Disorders ◽  
Inborn Errors ◽  
Lysosomal Disorders ◽  
Cycle Disorders ◽  
Cobalamin Disorders

Inborn errors of metabolism (IEM) are individually rare but have a collective incidence of approximately one in 1000. Most IEM can manifest with neurologic symptoms. It is crucial for the pediatric neurologist to be familiar with the evaluation and management of these disorders because many are amenable to specific treatments. This review provides a category-based approach to the diagnosis and treatment of IEM organized by metabolic pathway and organelle. Categories include disorders of mitochondrial fatty acid oxidation and carnitine metabolism, urea cycle disorders, organic acidemias, aminoacidopathies, lysosomal disorders, peroxisomal disorders, vitamin- and diet-responsive metabolic epilepsies, and neurotransmitter disorders. Multiple summary tables for quick reference are provided. Figures show mitochondrial β-oxidation and carnitine cycle; urea cycle; T2-weighted magnetic resonance images (MRI) of ornithine transcarbamylase deficiency presenting with hyperammonemic encephalopathy, propionic academia, methylmalonic academia, glutaric acidemia type 1, ethylmalonic encephalopathy, mitochondrial complex 1 deficiency, pyruvate dehydrogenase complex E3 deficiency, untreated biotin-thiamine-responsive basal ganglia disease, homocysteinemia and low plasma methionine (suspected remethylation defect), attenuated Krabbe disease, Hunter syndrome, and GM1-gangliosidosis; branched-chain amino acid catabolic pathway; lysine, hydroxylysine, and tryptophan catabolic pathway; intracellular cobalamin metabolism; metabolism of homocysteine; diffusion-weighted imaging of maple syrup urine disease, nonketotic hyperglycinemia, and poorly controlled phenylketonuria; sphingolipid metabolic pathway; skeletal surveys of Hurler syndrome demonstrating features of dysostosis multiplex and rhizomelic chondrodysplasia punctata type 1; MRI of Salla disease; peroxisomal oxidation reactions, and the biogenic amine biosynthetic pathway. Tables list fatty acid oxidation and carnitine disorders, metabolic myopathies presenting with recurrent rhabdomyolysis, urea cycle disorders, organic acidemias, IEM associated with abnormal head size, cobalamin disorders, aminoacidopathies, IEM associated with abnormal odor, lysosomal disorders, lysosomal disease Symptom categories (Not mutually exclusive), peroxisomal disorders, IEM associated with brain malformations, vitamin- and diet-responsive epilepsies, neurotransmitter disorders, and IEM associated with brain mineralization. This review contains 26 highly rendered figures, 15 tables, and 71 references. Key words: Inborn errors of metabolism, organic acidemia, cobalamin disorders, aminoacidopathy, lysosomal disorders

Valproate-induced fatal acute hyperammonaemia-related encephalopathy in late-onset ornithine transcarbamylase deficiency

2021 ◽  
Vol 14 (5) ◽  
pp. e241429
Author(s):  
Daniel Kazmierski ◽  
Nishant Sharma ◽  
Kelly O'Leary ◽  
Pius Ochieng
Keyword(s):  
Cerebral Oedema ◽  
Urea Cycle ◽  
Late Onset ◽  
Genetic Disorder ◽  
Management Strategies ◽  
Ornithine Transcarbamylase ◽  
Ornithine Transcarbamylase Deficiency ◽  
History Of ◽  
Otc Deficiency ◽  
Psychiatric Conditions

Ornithine transcarbamylase (OTC) deficiency is a genetic disorder of the urea cycle characterised by deficiency in the enzyme OTC, resulting in an accumulation of ammonia. Valproic acid (VPA), a commonly used medication in the treatment of neurologic and psychiatric conditions, has been known to cause episodes of acute hyperammonaemia in patients with OTC deficiency. We present the case of a 29-year-old man with a long history of non-specific psychiatric disorders, who suffered from a hyperammonaemic crisis following the administration of VPA, leading to the diagnosis of OTC deficiency. The patient’s hospital course was complicated by progressive cerebral oedema, which resulted in worsening encephalopathy, seizures and death. We discuss the pathophysiology of hyperammonaemia in OTC deficiency, and various management strategies, including lactulose, levocarnitine, scavenger therapy and haemodialysis.

scholarly journals Development and application targeted NGS panels in the selective screening algorithm for inborn errors of metabolism. An experience of the St. Petersburg Medical and Genetic Center

2020 ◽  
pp. 66-68
Author(s):  
Ю.А. Чурюмова ◽  
Н.В. Вохмянина ◽  
С.В. Шляга ◽  
Т.В. Вавилова ◽  
Т.С. Симакова ◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Clinical Symptoms ◽  
Genetic Diseases ◽  
Selective Screening ◽  
Inborn Errors ◽  
Leading Role ◽  
Childhood Morbidity ◽  
Screening Algorithm ◽  
Targeted Ngs ◽  
Biochemical Testing

Наследственные болезни обмена веществ представляют собой обширный класс генетических заболеваний и вносят значительный вклад в детскую заболеваемость, при этом их диагностика с использованием биохимических методов зачастую вызывает затруднения. В СПбГКУЗ МГЦ были разработаны и внедрены три панели для секвенирования 88 генов, ответственных за развитие трех групп наследственных болезней обмена (НБО), и протестировано 84 ребенка, у которых данные заболевания были заподозрены по данным тандемной масс-спектрометрии (ТМС), либо по наличию клинических симптомов. У 6 детей методом NGS полностью установлена генетическая причина заболевания. Патогенные мутации выявлялись значительно чаще при повышении биохимических маркеров, демонстрируя ведущую роль предварительного биохимического скрининга в проведении NGS анализа. NGS значительно повышает результативность клинической диагностики НБО. Биохимическое тестирование и NGS играют взаимодополняющие роли, и их комплексное использование в алгоритме селективного скрининга позволяет повысить точность диагностики НБО. Inborn errors of metabolism are an extensive class of genetic diseases and contribute significantly to childhood morbidity, and their diagnosis using biochemical methods is often difficult. Three panels for sequencing of 88 genes responsible for the development of three groups of inborn errors of metabolism (IEM) were developed and introduced in St.Petersburg Medical and Genetic Center and 84 children were tested for which these diseases were suspected by tandem mass-spectrometry or by the presence of clinical symptoms. In 6 children, the NGS method fully established the genetic cause of the disease. Pathogenic mutations were detected significantly more frequently with increased biochemical markers, demonstrating the leading role of pre-biochemical screening in performing NGS analysis. NGS significantly improves the clinical diagnostic effectiveness of IEM. Biochemical testing and NGS play complementary roles and their complex use in selective screening algorithm allows to increase accuracy of IEM diagnostics.

scholarly journals The Mechanism of Hyperammonemia Triggered by Corticosteroid Administration in Late-Onset Ornithine Transcarbamylase Deficiency

2021 ◽  
Author(s):  
Koji Imoto ◽  
Masatake Tanaka ◽  
Takeshi Goya ◽  
Tomoko Aoyagi ◽  
Motoi Takahashi ◽  
...  
Keyword(s):  
Brain Injuries ◽  
Urea Cycle ◽  
Late Onset ◽  
Ornithine Transcarbamylase ◽  
Ornithine Transcarbamylase Deficiency ◽  
Adult Onset ◽  
Loss Of Function ◽  
Carbamoyl Phosphate ◽  
Gene Expressions ◽  
Corticosteroid Administration

Abstract Background: Ornithine transcarbamylase deficiency (OTCD) is most popular among urea cycle disorders (UCDs), defined by the loss of function in any of the enzymes associated with ureagenesis. Corticosteroid administration to UCD patients, including OTCD patients, is well known to induce life-threatening hyperammonemia. The mechanism has been considered nitrogen overload due to the catabolic effect of corticosteroids; however, the pathophysiological process is unclear. We evaluated the effects of corticosteroids on urea cycle enzyme expressions and urea cycle-associated metabolites in OTC-deficient mice.Methods: The clinical courses of two adult-onset OTCD patients were presented. To elucidate the mechanism of hyperammonemia induced by corticosteroid administration in OTCD patients, we developed a mouse model by administering corticosteroids to OTCspf-ash mice deficient in the OTC gene. Dexamethasone (DEX; 20 mg/kg) was administered to the OTCspf-ash and wild-type (WT) mice at 0 and 24 h, and the serum ammonia concentrations, the levels of the hepatic metabolites, and the gene expressions of urea-cycle-related genes were analyzed.Results: Two adult-onset OTCD patients received multimodal treatment, including dialysis, and recovered completely from severe hyperammonemia. The ammonia levels in Otcspf-ash mice that were administered DEX tended to increase at 24 h and increased significantly at 48 h. The metabolomic analysis showed that the levels of citrulline, arginine, and ornithine did not differ significantly between Otcspf-ash mice that were administered DEX and normal saline; however, the level of aspartate was increased drastically in Otcspf-ash mice owing to DEX administration (P < 0.01). Among the enzymes associated with the urea cycle, mRNA expressions of carbamoyl-phosphate synthase 1, ornithine transcarbamylase, arginosuccinate synthase 1, and arginosuccinate lyase were significantly downregulated by DEX administration in both the Otcspf-ash and WT mice (P < 0.01).Conclusions: We elucidated that corticosteroid administration induced hyperammonemia in Otcspf-ash mice by suppressing urea-cycle-related gene expressions as early as 24 h. Since the urea cycle intermediate amino acids, such as arginine, might not be effective because of the suppressed expression of urea-cycle-related genes by corticosteroid administration, we should consider an early intervention by renal replacement therapy in cases of UCD patients induced by corticosteroids to avoid brain injuries or fatal outcomes.

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